# Sex-Stratified Skeletal Treatment Effects from the INVEST in Bone Health Randomized Clinical Trial

## TL;DR

This study found that adding a weighted vest to weight loss helped older women reduce bone loss, but had different effects in men.

## Contribution

The study reports sex-specific skeletal treatment effects of weight loss interventions in older adults.

## Key findings

- In women, WL+VEST reduced total hip vBMD loss and increased bone formation marker P1NP.
- In men, WL+VEST worsened femoral neck aBMD loss compared to weight loss alone.
- Weight loss plus resistance training also increased P1NP in women.

## Abstract

The main goal of the INVEST in Bone Health Trial (NCT04076618) was to compare effects of weight loss (WL) alone (caloric restriction targeting 10% WL), WL plus weighted vest use (WL+VEST; 8 hours/day, weight replacement titrated up to 10% total WL), or WL plus progressive resistance training (WL+RT; 3 supervised sessions/week) on bone health indicators in older adults. As women are more likely to develop osteoporosis and experience fractures, the purpose of this secondary analysis was to present 12-month skeletal treatment effects [including: volumetric bone mineral density (vBMD), areal (a)BMD, and biomarkers of bone turnover (procollagen type 1 N-terminal propeptide (P1NP) and C-terminal cross-linked telopeptide (CTX))] stratified by sex. 150 (74.7% women) older adults (66.4±4.6 years; 68.6% White) living with overweight or obesity (BMI: 33.6±3.3kg/m2) were randomized (n = 50/group) with 133 (89%) completing the trial. Baseline age, weight, height, cardiovascular disease prevalence, and physical activity energy expenditure were higher in men than women. No sex differences were noted in intervention compliance (e.g., weight loss, vest wear-time, RT session attendance). In women, WL+VEST attenuated total hip vBMD loss [estimated treatment difference (ETD): +0.0019 mg/cm3 (0.0005, 0.0034); p = 0.008] and increased P1NP [ETD: +7.6 µg/L (0.8, 14.3); p = 0.014] versus WL alone. WL+RT also increased P1NP versus WL alone [ETD: +5.3 µg/L (-0.3, 10.9); p = 0.028] in women. Conversely, in men WL+VEST exaggerated femoral neck aBMD loss versus WL alone [ETD: -0.038 g/cm2 (-0.066, -0.009); p = 0.012]. In older women, but not men, undergoing caloric restriction, weighted vest use may reduce bone loss via increased bone formation.